"Our laboratory investigations are focused on identifying genes that regulate growth, differentiation, and programmed cell death of normal and malignant mammary epithelial cells in order to develop rational strategies for the treatment of breast cancer. We have several ongoing projects: (1) We have cloned cbl-b and cbl-3, two new mammalian proteins with homology to the c-cbl proto-oncogene. cbl proteins are novel signal transduction molecules downstream of receptor tyrosine kinases. Studies in the nematode C. elegans suggest that the cbl homologue is a suppressor of epidermal growth factor receptor (EGFR) signaling. Ongoing work is focused on elucidating the role that cbl proteins play in the growth stimulation mediated by the EGF family of receptor tyrosine kinases in mammary epithelial cells. We have demonstrated that cbl-b and cbl-3 associate with the EGF receptor and inhibit signaling and are now investigating the biochemical mechanisms of this inhibition. (2) We are investigating the expression and function of death receptors of the TNFR family (e.g. TNFR, Fas, Dr3, Dr4, and Dr5) in normal and malignant breast epithelial cells. Ongoing projects are focused on exploring the normal physiologic role of the death receptors in mammary epithelial cells, the relationship of malignant transformation and the death receptor pathways, and the modulation of these pathways in breast cancer cells in vitro and in vivo."